GENE THERAPY FOR CYSTIC FIBROSIS USING CATIONIC LIPOSOME MEDIATED GENE TRANSFER

使用阳离子脂质体介导的基因转移治疗囊性纤维化

• 批准号: 6274050
• 负责人: Eric J SORSCHER
• 金额: $ 2.59万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-26 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6274050
• 关键词: chloride channels; clinical research; clinical trial phase I; cystic fibrosis; gene targeting; gene therapy; human subject; human therapy evaluation; liposomes; polymerase chain reaction; tissue /cell culture; transfection

Transfer of normal human CFTR to human CF epithelial cells, respiratory epithelium of CF mice, or human nasal airways (using adenoviral vectors) may lead to re-establishment of CFTR mediated chloride transport. Gene transfer mediated correction of the CF bioelectric defect in these model systems indicate the importance of investigating gene transfer-based protocols in the disease. In the present protocol, we evaluate a cationic liposome-based mechanism of delivery of normal CFTR to nasal respiratory epithelia of CF patients. Patients undergo one-time administration of a single dose of a lipid/DNA formulation containing DMRIE/DOPE (lipid) and plasmid DNA encoding the full length CFTR. To date, we have studied three patients and the results have been encouraging. Successful gene transfer was observed in two of three patients, and no evidence of toxicities or side effects were observed in the nasal airways, lung, or other organ systems. Because of these encouraging findings, we intend to study six additional patients in the near future.

将正常人CFTR转移至人CF上皮细胞，呼吸道 CF小鼠或人鼻气道的上皮（使用腺病毒载体） 可能导致CFTR介导的氯离子转运的重建。 基因 这些模型中CF生物电缺陷的转移介导校正 系统表明研究基于基因转移的 在疾病中的协议。在本协议中，我们评估了阳离子 正常CFTR递送至鼻呼吸道的基于脂质体的机制 CF患者的上皮细胞。 患者接受一次性给药， 单剂量的含有DMRIE/DOPE（脂质）的脂质/DNA制剂和 编码全长CFTR的质粒DNA。到目前为止，我们已经研究了三个 病人和结果是令人鼓舞的。成功的基因转移 在三名患者中的两名中观察到，没有毒性或 在鼻气道、肺或其他器官中观察到副作用 系统. 由于这些令人鼓舞的发现，我们打算研究六个 在不久的将来，更多的病人。